Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients

NCT01346787 | Completed Phase 2 DMC

• 1 other identifier: IST-CAR-506
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 13

Brief Summary

The purpose of this study is to determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed Multiple Myeloma (MM).

Conditions

Multiple Myeloma

Keywords

carfilzomib; dexamethasone; cyclophosphamide; multiple myeloma; newly diagnosed

Outcome Measures

Primary Outcomes (2)

• Toxicity: Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0)

  Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity excluding anemia, (grade 4 neutropenia must last longer than 3 days and grade 4 thrombocytopenia must last longer than 7 days in order to be considered a toxicity) with the exception of (grade 4 neutropenia \> 3 days , or grade 4 thrombocytopenia \>7 days duration) or grade 3 non-hematologic drug-related toxicity.

  4 years

• Efficacy will be assessed by considering partial response (PR) following the proposed regimen. Assessment of Partial Response rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group.

  4 years

Secondary Outcomes (15)

• Response rate

  4 years

• Duration of Progression Free Survival

  4 years

• Time to progression (TTP)

  4 years

• Duration of Response (DOR)

  4 years

• Duration of Overall Survival

  4 years

Study Arms (1)

Carfilzomib Cyclophosphamide Dexamethasone

EXPERIMENTAL

The treatment period includes administration of Carfilzomib Cyclophosphamide Dexamethasone for 9 courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled carfilzomib administration. The response will be assessed after each cycle.

Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE

Interventions

CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE DRUG

Patients will start induction treatment with Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. Low dose Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23. Carfilzomib = 20 mg/m2 IV once daily on days 1, 2, of cycle 1 only followed by 36 mg/ m2 days 8, 9, 15, 16 in cycle 1, then for all subsequent doses 36 mg/ m2 IV once daily on days 1, 2, 8, 9, 15, 16, followed by 13-day rest period (day 17 through 28). Each cycle will be repeated every 28 days for a total of 9 courses. MANTEINANCE PERIOD At the end of induction phase (9 courses), maintenance phase with Carfilzomib alone IV at 36 mg/ m2 IV on days 1, 2, 15, 16 will start, until progression or intolerance. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator, or the patient may be removed from the study

Carfilzomib Cyclophosphamide Dexamethasone

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patient is of a legally consenting age as defined by local regulations.
• Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation.
• Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
• Patient is a newly diagnosed MM patient.
• Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results.
• \- Patient has a Karnofsky performance status ≥60%.
• Patient has a life-expectancy \>3 months.
• Patient has the following laboratory values within 14 days before Baseline (day
• of the Cycle 1, before study drug administration):
• Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to drug administration).
• Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors.
• Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)

You may not qualify if:

• \- Patients with non-secretory MM, unless serum free light chains are present and the ratio is abnormal.
• Pregnant or lactating females
• Patient has active infectious hepatitis type B or C or HIV.
• Patients with myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Known history of allergy to Capsidol (a cyclodextrin derivative used to solubilize carfilzomib)
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
• Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to baseline;
• Patient has any other clinically significant illness that would, in the investigator's opinion, increase the patient's risk for toxicity.
• Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score \<7 with a stable PSA)

Sponsors & Collaborators

• European Myeloma Network B.V.: lead
• Fondazione EMN Italy Onlus: collaborator

Study Sites (13)

IRCCS CROB UOC di Ematologia e trapianto cellule staminali Ospedale Oncologico Regionale

Rionero in Vulture, PZ, 85100, Italy

Location

azienda ospedaliero-universitaria umberto I Clinica di Ematologia

Ancona, 60020, Italy

Location

Policlinico S. Orsola Istituto di Ematologia e Oncologia Medica

Bologna, 40138, Italy

Location

Ospedale Ferrarotto_Reparto di Ematologia

Catania, 95124, Italy

Location

Az.Osp. Di Careggi_Dh ematologia

Florence, 50134, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori_UO Ematologia_Trapianto di Midollo Osseo Allogenico

Milan, 20133, Italy

Location

Divisione di Ematologia Dipartimento di Medicina Clinica e Sperimentale Università Amedeo Avogadro

Novara, 28100, Italy

Location

Cattedra di ematologia Università La Sapienza

Roma, Italy

Location

Divisione di Ematologia Ospedale S. Eugenio

Roma, Italy

Location

S.C.di Oncoematologia, Azienda Ospedaliera S. Maria di Terni

Terni, Italy

Location

SC Ematologia - A.O.U. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

SSD CLINICAL TRIAL IN ONCOEMATOLOGIA E MIELOMA MULTIPLO - A.O.U. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Erasmus MC

Rotterdam, Netherlands

Location

Related Publications (5)

• Mina R, Bonello F, Petrucci MT, Liberati AM, Conticello C, Ballanti S, Musto P, Olivieri A, Benevolo G, Capra A, Gilestro M, Galieni P, Cavo M, Siniscalchi A, Palumbo A, Montefusco V, Gaidano G, Omede P, Boccadoro M, Bringhen S. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies. Haematologica. 2021 Apr 1;106(4):1079-1085. doi: 10.3324/haematol.2019.243428.

  PMID: 32107329 DERIVED

• Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.

  PMID: 31221778 DERIVED

• Bringhen S, Mina R, Petrucci MT, Gaidano G, Ballanti S, Musto P, Offidani M, Spada S, Benevolo G, Ponticelli E, Galieni P, Cavo M, Di Toritto TC, Di Raimondo F, Montefusco V, Palumbo A, Boccadoro M, Larocca A. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies. Haematologica. 2019 Aug;104(8):1640-1647. doi: 10.3324/haematol.2018.208272. Epub 2019 Feb 7.

  PMID: 30733270 DERIVED

• Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.

  PMID: 25628469 DERIVED

• Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omede P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. doi: 10.1182/blood-2014-03-563759. Epub 2014 May 22.

  PMID: 24855212 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: May 3, 2011
• Study Start: July 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: May 31, 2023
• Last Updated: September 8, 2023

Record last verified: 2023-09

Locations

IT (12); NL (1)